My enthusiasm for biological research was kindled during my final year of study in Manchester working on my lab project stidying biological clocks with Professor Andrew Loudon. This led me to continue academic study by enrolling for a masters degree in UCL. I undertook this part-time, funding myself through various part-time jobs. The masters laboratory project was with Dr John Scholes with whom I studied the microglial reaction in the facial nucleus of the mouse hindbrain following facial nerve axotomy, we investigated how ‘static’ ramified microglia proliferate and migrate to the nucleus. The studies were a first chance for me to examine the microstructure of the brain first hand, something that I was keen to continue and I applied for and won a departmental MRC studentship to study for a Ph.D. with Dr Scholes.

My Ph.D. project was quite different from the masters work: I examined the control of CNS myelination using carp optic nerve regeneration/remyelination as the model system. Through various surgical manipulations of the optic nerve and optic tectum – its principle brain target – I showed that the optic axons must first form synaptic connections with the target tissue before they are myelinated.

During the last year of laboratory study in Dr Scholes’ laboratory I began a collaboration with Dr Pavlina Haramis and Professor Stephen Wilson studying a zebrafish mutant called akineto. The phenotype of the mutant is a lack of movement and I determined that this was caused by missing thick filaments in the sarcomeres of the skeletal muscle. After submitting my thesis, but before doing my viva, I won a bogue research fellowship to travel to the USA and study this mutant further. I went to the laboratory of Professor William Talbot in Stanford University, California. Whilst in Prof. Talbot’s lab I did further mapping of this mutant, homing in on the genomic location of the lesion. I also assisted in their screen for myelination mutants by studying some of the mutants using electron microscopy. After returning to the UK I continued working on the akineto mutant, discovering the phenotype to be cause by a lesion in the Hsp90a gene. Following this finding I opened up collaborations with several other laboratories to investigate the consequences of the mutation. The study was accepted for publication in 2007, published early 2008 (see below)

Current project.

Since 2004, concurrent with finishing the study of the akineto mutant I have been co-supervised by Steve Wilson and Jon Clarke, working closely with Monica Folgueira and Kate Turner in the lab on an important long-term project: the construction of an online atlas of zebrafish developmental neuroanatomy. Details of the project can be found on the research pages of the website, but I will give a brief desciption here. This exciting and ambitious project was started as our contribution to the ZF-MODELS EU-wide project to develop zebrafish as a model organism. Our part of the project was to aid in the interpretation of brain expression patterns generated by the laboratories undertaking large-scale enhancer/expression screens. Through imaging the expression of GFP in multiple transgenic lines and double staining with antibodies we generated an extensive library of confocal images of these lines and others which highlighted discrete areas in the brain. The delineation of particular brain nuclei and tracts by the transgenic lines was used to form the basis for an atlas of brain development. A database of the images has been constructed and ‘tutorials’ which pull together data descibing specific brain structures are being written. We have also begun the development of a multidimensional navigational tool to allow intuitive interactive viewing of the zebrafish brain. The images, tutorials and navigational tool together form the online atlas.

The first launch of the atlas will take place in 2009, this will initially be released to select members of the zebrafish comunity for feedback. following this, a full version will then be made freely available to the wider comunity. This initial atlas will be somewhat of a pilot version: it will have a solid back-end database and it will contain high resolution data on many brain areas but fine detail will not be available on all brain areas and the navigational tools may not be entirely complete. We are currently working to secure further funding for the atlas project to allow us to expand the coverage of the atlas to fine deatail of the whole brain. To do this we plan to image a large slection of novel transgenics from various ongoing large-scale transgenesis projects around the world. We also plan to further develop the bioinformatic navigational tools and to custom-design some tarnsgenics specifically for the atlas. In the production of the transgenics we will employ the Gal4/UAS system (or similar) to allow for them to be used with other transgenics for further imaging/behavioural studies. This opens up the exciting prospect of being able to present highly detailed information on subsets of neurones which subsequently can be live-imaged (using aqueorin or similar) or knocked-out and the behavioural consequences examined.

Our long-term vision is for the atlas to become an essential community resource: acting as a repository for all neuroanatomical information on the zebrafish.